Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers such as hematoporphyrin derivative (HPD) and other compounds to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in their metastable singlet delta state O2 (1delta) are believed to be the species that destroys cancerous cells during PDT. A real-time optical diagnostic for singiet oxygen in-vivo would be a valuable dosimeter during PDT treatment. Based on a successful Phase I program, Physical Sciences Inc. proposes to develop and test a real-time optical monitor for singlet oxygen. We will use diode laser technology and ultra-sensitive photon counting methods. Extensive in-vitro testing will be performed using several photosensitizers. Crucial in-vivo tests will also be performed on tumor models in laboratory rats. These tests will be performed with our collaborators at the Massachusetts General Hospital. Success will lead to a product for medical research in PDT. The successful demonstration of the diagnostic could lead to numerous applications. For example, one could study the photo-induced HPD process in much more detail. New porphyrin compounds could be screened for O2 (1delta) production efficiency. Finally a real time O2 (1delta) monitor during phototherapy could be an invaluable tool for improving the efficiency of cancer cell destruction.